Animal nerve systems (including those that drive muscular and cardiac functions), and more particularly those of relatively complex living creatures such a mammals and yet more specifically, of humans; can contain thousands of nerve cells packed closely together and firing in various ways (e.g., frequencies, strengths, concurrencies, mutual exclusivities, etc.) depending on underlying states of the corresponding nervous system. Such activities can be monitored in vivo invasively by penetrating through skin and/or skull and electrically (or electro-optically) coupling directly to individual nerve cells. However, such invasive techniques have their drawbacks, particularly in cases where the subject is relatively healthy and invasive procedure is not otherwise called for.
Invasive determination of neuronal activity often entails use of linear bio-current detecting or linear bio-potential detecting devices respectively having a linear and highly sensitive current amplifier or a linear and highly sensitive voltage amplifier, sometimes in respective combination with a linear current-to-voltage converter or a linear voltage-to-current converter. The linear signal inputting device of such methods is typically connected by way of relatively long wires to corresponding probes or electrodes that make contact with the biological specimen under study. For example, in conventional, current-based electrophysiology setups, a biocompatible conducting electrode (e.g., silver, silver chloride, tungsten, or stainless steel) is placed near to a group of neurons or directly inserted into a specific nerve cell. Often, glass pipettes containing the conducting electrode material are inserted inside the neurons. The electrode is electrically coupled by way of a conducting wire to a head input stage of the electrical detection system (for example for linear signal pre-amplification and/or for linear impedance transformation such as from high impedance (e.g., >1K ohm) to low impedance). The head input stage then drives a high-fidelity and linear operational amplifier (for example a circuit having field effect transistors (FET) operating in the linear portions of their IN characteristics). Such high-fidelity and linear input devices tend to be expensive, bulky in size and difficult to integrate into the form of monolithic integrated circuits (IC's). After the received signal is amplified via the front-end high-fidelity and linear input amplifier, various analog signal filtering processes may take place, followed by optional conversion to digital format and further processing by data processing units for example by application to customized spike-sorting algorithms so as to identify meaningful ones among the many neural events that generally take place in the Animal System Under Study (ASUS).
By way of another example, in conventional, voltage-based electrophysiology measurement setups, electrical potential is measured as between two spaced apart points of the animal system under study (ASUS) with one electrode sensing potentials at a predetermined point of interest while the other serves as a reference point (e.g., a reference ground). In this conventional amplification configuration of linearly detecting differential voltages, the meaningful signal that one can detect typically must be at least 10 μV RMS if not more in strength and with a bandwidth in the low kHz range. Due to this limit on conventional electrophysiology, weaker signals below the 10 μV RMS minimum range can only be acquired by use of extensive signal averaging techniques. Even with such extensive signal averaging, it is challenging to identify significant neural events (firings of isolated single cells, or of specific groups of nerve cells or changes in global brainwave activity) because the averaging process tends to bury the significant neural events within the encompassing average of all events. Accordingly, the signals of interest are often lost and cannot be usefully studied or applied for associated purposes.
In academic neuroscience studies, one often follows a laborious process of puncturing cells (patch recording) in order to obtain low-level signals from individual neurons. This procedure usually does not maintain the health of the cells for a long time, nor can it be scaled up for high-throughput drug or other health screening programs. Efforts that were made to reduce the noise introduced by the electronics entail extreme measures such as super cooling of the pre-amplifier stage. Measuring neuronal signals in the brain without puncturing the cells, and attempts at measuring extra-cellular signals result in a lot of noise. Signals below the 1 μV range measured with high-input-resistance electrodes (˜1 MΩ or greater) sometimes sink into the noise floor and require extensive signal averaging to overcome noise problems. But then the averaging process itself buries the signal of interest. In addition, when measuring neuronal activities in vivo in intact neurons by placing the electrode near a neuron, the environmental noise tends to be even larger than that experienced for an in vitro lab situation.
Some commercially available electrophysiology machines or multi-electrode arrays (MEA) may be used for drug discovery research. However, while these machines allow measurements to be taken without puncturing the cells and the number of cells easily scale up, they are difficult to use because growing primary neurons in an artificial setting is difficult, and the sensitivity (the signal-to-noise ratio) of these devices is not optimal for characterizing and distinguishing individual neurons. Also, the secondary current effects from the metal surfaces not directly from cells can often create interference. Finally, these devices are extremely bulky, making it difficult to design flexible experiments that can be conveniently carried out by patients (or other subjects, e.g., animal study subjects) of a corresponding clinical trial.
For physician's use, while nearly 100 million people are affected by a brain or nervous system disorder in the United States alone, the devices physicians generally use for dealing with the various disorders suffer from various limitations. For example, current electrophysiology or electroencephalogram (EEG) systems for clinical and surgical (intra-operative) applications are still noisy. Monitoring patients based on evoked potentials (around 10 μV) from an intra-operative EEG requires extensive signal averaging. Furthermore, current hospital and ambulatory EEG devices require wet electrodes, which are not always convenient to use. Although portable EEG devices that utilize dry electrodes may be available, they do not yield any better signal-to-noise ratio than the widely used EEG devices with their wet electrodes. Moreover, long-term monitoring EEG devices used by hospitals tend to be bulky. More critically, there is currently no high fidelity, noninvasive EEG device that can predict abnormal nervous system events from current events and thus provide long-term diagnostic functions.
Factors such as lower signal quality, bulkiness and higher power consumption can hinder designing more flexible experiments for animals or human subjects. Thus, a compact device that yields substantially higher signal-to-noise ratio of neural events that can be measured non-invasively and with low power consumption would play a tremendous role in moving forward the field of neuroscience/neuromedicine. This concept can be further extended to electrophysiology, electroencephalogram, cardiology, and/or electromyography systems.
It is to be understood that this background of the technology section is intended to provide useful background for understanding the here disclosed technology and as such, the technology background section may include ideas, concepts or recognitions that were not part of what was known or appreciated by those skilled in the pertinent art prior to corresponding invention dates of subject matter disclosed herein.